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Background: A number of the deeper divergences in the placental mammal tree are still inconclusively resolved despite extensive phylogenomic analyses. A recent analysis of 200 kbp of protein coding sequences yielded only limited support for the relationships among Laurasiatheria (cow, dog, bat and shrew), probably because the divergences occurred only within a few million years from each other. It is generally expected that increasing the amount of data and improving the taxon sampling enhance the resolution of narrow divergences. Therefore these and other difficult splits were examined by phylogenomic analysis of the hitherto largest sequence alignment. The increasingly complete genome data of placental mammals also allowed developing a novel and stringent data search method. Results: The rigorous data handling, recursive BLAST, successfully removed the sequences from gene families, including those from well-known families hemoglobin, olfactory, myosin and HOX genes, thus avoiding alignment of possibly paralogous sequences. The current phylogenomic analysis of 3,012 genes (2,844,615 nucleotides) from a total of 22 species yielded statistically significant support for most relationships. While some major clades were confirmed using genomic sequence data, the placement of the treeshrew, bat and the relationship between Boreoeutheria, Xenarthra and Afrotheria remained problematic to resolve despite the size of the alignment. Phylogenomic analysis of divergence times dated the basal placental mammal splits at 95–100 million years ago. Many of the following divergences occurred only a few (2–4) million years later. Relationships with narrow divergence time intervals received unexpectedly limited support even from the phylogenomic analyses. Conclusion: The narrow temporal window within which some placental divergences took place suggests that inconsistencies and limited resolution of the mammalian tree may have their natural explanation in speciation processes such as lineage sorting, introgression from species hybridization or hybrid speciation. These processes obscure phylogenetic analysis, making some parts of the tree difficult to resolve even with genome data.
Prolonged treatment of leukemic cells with chemotherapeutic agents frequently results in development of drug resistance. Moreover, selection of drug-resistant cell populations may be associated with changes in malignant properties such as proliferation rate, invasiveness, and immunogenicity. In the present study, the sensitivity of cytarabine (1-β-d-arabinofuranosylcytosine, araC)-resistant and parental human leukemic cell lines (T-lymphoid H9 and acute T-lymphoblastic leukemia Molt-4) to natural killer (NK) cell-mediated killing was investigated. The results obtained demonstrate that araC-resistant H9 and Molt-4 (H9rARAC100 and Molt-4rARAC100) cell lines are more sensitive to NK cell-mediated lysis than their respective parental cell lines. This increased sensitivity was associated with a higher surface expression of ligands for the NK cell-activating receptor NKG2D, notably UL16 binding protein-2 (ULBP-2) and ULBP-3 in H9rARAC100 and Molt-4rARAC100 cell lines. Blocking ULBP-2 and ULBP-3 or NKG2D with monoclonal antibody completely abrogated NK cell lysis. Constitutive phosphorylated extracellular signal-regulated kinase (ERK) but not pAKT was higher in araC-resistant cells than in parental cell lines. Inhibition of ERK using ERK inhibitor PD98059 decreased both ULBP-2/ULBP-3 expression and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in H9 parental cells resulted in increased ULBP-2/ULBP-3 expression and enhanced NK cell lysis. These results demonstrate that increased sensitivity of araC-resistant leukemic cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway.
Requirements for the interaction of mouse Polkappa with ubiquitin and its biological significance
(2008)
Polkappa protein is a eukaryotic member of the DinB/Polkappa branch of the Y-family DNA polymerases, which are involved in the tolerance of DNA damage by replicative bypass. Despite universal conservation through evolution, the precise role(s) of Polkappa in this process has remained unknown. Here we report that mouse Polkappa can physically interact with ubiquitin by yeast two-hybrid screening, glutathione S-transferase pulldown, and immunoprecipitation methods. The association of Polkappa with ubiquitin requires the ubiquitin-binding motifs located at the C terminus of Polkappa. In addition, Polkappa binds with monoubiquitinated proliferating cell nuclear antigen (PCNA) more robustly than with non-ubiquitinated PCNA. The ubiquitin-binding motifs mediate the enhanced association between monoubiquitinated PCNA and Polkappa. The ubiquitin-binding motifs are also required for Polkappa to form nuclear foci after UV radiation. However, the ubiquitin-binding motifs do not affect Polkappa half-life. Finally, we have examined levels of Polkappa expression following the exposure of mouse cells to benzo[a]pyrene-dihydrodiol epoxide or UVB radiation.
Background One of the central issues in ecology is the question what allows sympatric occurrence of closely related species in the same general area? The non-biting midges Chironomus riparius and C. piger, interbreeding in the laboratory, have been shown to coexist frequently despite of their close relatedness, similar ecology and high morphological similarity. Methodology/Principal Findings In order to investigate factors shaping niche partitioning of these cryptic sister species, we explored the actual degree of reproductive isolation in the field. Congruent results from nuclear microsatellite and mitochondrial haplotype analyses indicated complete absence of interspecific gene-flow. Autocorrelation analysis showed a non-random spatial distribution of the two species. Though not dispersal limited at the scale of the study area, the sister species occurred less often than expected at the same site, indicating past or present competition. Correlation and multiple regression analyses suggested the repartition of the available habitat along water chemistry gradients (nitrite, conductivity, CaCO3), ultimately governed by differences in summer precipitation regime. Conclusions We show that these morphologically cryptic sister species partition their niches due to a certain degree of ecological distinctness and total reproductive isolation in the field. The coexistence of these species provides a suitable model system for the investigation of factors shaping the distribution of closely related, cryptic species.
In 2007, a project named Adriatic Montenegro 2007 was initiated and realised under the protection of IDF. Stimulated by the suggestion of Vincent Kalkman from the European Invertebrate Survey, The Netherlands, distribution data for the Odonata of Adriatic Montenegro were collected and used to create distribution maps. These data and maps should then be used in the evaluation of conservation measures for individual odonate species as well as for the IUCN Red List of the Mediterranean countries (organized by the IUCN Centre for Mediterranean Cooperation) and the Project on an atlas of European dragonflies (a co-operation of all European countries organised by the European Invertebrate Survey, The Netherlands).
It has been suggested that the existence of a non-Gaussian fixed point in general relativity might cure the ultraviolet problems of this theory. Such a fixed point is connected to an effective running of the gravitational coupling. We calculate the effect of the running gravitational coupling on the black hole production cross section in models with large extra dimensions.
Religious conversion has become a dangerous social and individual problem. In Latin America, a traditional Catholic area, Protestant sects are successfully con-verting more and more Catholics into their own communities. Therefore the Pope demands a strict control of these activities. In India e.g., the Catholic hierarchy is critizising the Indian governments which have forbidden conversion on non-spiritual reasons. Hindu organizations have started even very successfully to re-convert Indian Christians particularly of Dalit and tribal background. Buddhists are very successful in indirect and even direct conversion of many Westerners. Wah-habit missionaries spread their Neo-Islam in the Muslim societies and get more and more even non-Muslim converts. We should add the forcible and sometimes ex-tremely cruel conversions the atheistic states had executed since the last century. ...
Background Medical students come into contact with infectious diseases early on their career. Immunity against vaccine-preventable diseases is therefore vital for both medical students and the patients with whom they come into contact. Methods The purpose of this study was to compare the medical history and serological status of selected vaccine-preventable diseases of medical students in Germany. Results The overall correlation between medical history statements and serological findings among the 150 students studied was 86.7 %, 66.7 %, 78 % and 93.3 % for measles, mumps, rubella and varicella, conditional on sufficient immunity being achieved after one vaccination. Conclusions Although 81.2 % of the students medical history data correlated with serological findings, significant gaps in immunity were found. Our findings indicate that medical history alone is not a reliable screening tool for immunity against the vaccine-preventable diseases studied.
Ataxin-2 is a novel protein, within which the unstable expansion of a polyglutamine domain can cause Spinocerebellar Ataxia type 2 (SCA2), a neurodegenerative disease which belongs to the group of polyglutamine disorders. SCA2 is characterised by a progressive loss of neurons that first affects the cerebellum and brain stem and then may extend to other areas of the brain, like substantia nigra, motoneurons and thalamus. Several lines of research have attempted to determine therole of ataxin-2 in its normal and mutant version. Different animal models and cell culture approaches to study ataxin-2 function implicated ataxin-2 in RNA processing, embryonic development, apoptosis and cytoskeleton. However, the function of ataxin-2 still remains unclear. In this thesis, a protein interaction approach was chosen as an alternative to gain insights into the cellular function of ataxin-2. Full-length ataxin-2 was used as bait in a yeast two-hybrid screen of human adult brain cDNA. Among five candidate interactor proteins identified, two were the endophilins A1 and A3, proteins involved in vesicle endocytosis. Co-immunoprecipitation studies confirmed the association of these proteins in an endogenous complex of mouse brain. In vitro binding experiments narrowed the binding interfaces down to two proline-rich domains on ataxin-2, which interacted with the SH3 domain of endophilins A1/A3. Ataxin-2 and endophilins A1/A3 colocalised at the endoplasmic reticulum as determined by immunofluorescence microscopy of transfected cell lines, and by centrifugation fractionation studies of mouse brain. Importantly, the pattern observed in transfected cells was conserved in untransfected rat hippocampal neurons. In mouse brain, associations of ataxin-2 with endocytic proteins such as the adaptor CIN85, the ubiquitin ligase c-Cbl and also GRB2, in the last case by means of a SH3 domain array chip, were also demonstrated. GST pull-down assays showed ataxin-2 to interact directly with the SH3 domains A and C of CIN85, the C-terminal SH3 domain of GRB2, and the SH3 domain of Src, a kinase activated after receptor stimulation. Functional studies demonstrated that ataxin-2 affects endocytic trafficking of the epidermal growth factor receptor (EGFR) by reducing the EGFR internalisation after EGF stimulation. Taken together, these data implicate ataxin-2 to play a role in endocytic receptor cycling.
The moderate halophile Halobacillus halophilus is the paradigm for chloride dependent growth in prokaryotes. Recent experiments shed light on the molecular basis of the chloride dependence that is reviewed here. In the presence of moderate salinities Halobacillus halophilus mainly accumulates glutamine and glutamate to adjust turgor. The transcription of glnA2 (encoding a glutamine synthetase) as well as the glutamine synthetase activity were identified as chloride dependent steps. Halobacillus halophilus switches its osmolyte strategy and produces proline as the main compatible solute at high salinities. Furthermore, Halobacillus halophilus also shifts its osmolyte strategy at the transition from the exponential to the stationary phase where proline is exchanged by ectoine. Glutamate was found as a second messenger" essential for proline production. This observation leads to a new model of sensing salinity by sensing the physico-chemical properties of different anions.
In this thesis I have investigated the regulation of eicosanoid synthesizing-enzymes by cannabinoid receptor agonists. Rat renal mesangial cells were used as a model system. I could show that all three (CB1, CB2, and GPR55) cannabinoid receptors are expressed on the mRNA level in rat renal mesangial cells – but with differing expression profiles. The CB1 and GPR55 receptors are expressed in comparable amounts, whereas the CB2 receptor is considerably less expressed than the CB1 and the GPR55 receptors. Furthermore I could show that stimulation of renal mesangial cells with CB1 receptor agonists, such as R(+)MA or ACEA, increased IL-1β-induced cPLA2, sPLA2-IIa, and COX2 protein and mRNA expression which subsequently led to an enhanced IL-1β-induced PGE2 formation. Additionally, the IL-1β- induced sPLA2-IIa promoter activity was also increased by CB1 receptor stimulation. Besides the modulated expression of the eicosanoid synthesizing enzymes, I could show that CB1 agonists also led to an increase of IL-1β-induced iNOS expression and subsequent NO formation. In contrast, stimulation with CB2 selective agonists led to a decrease in IL-1β- induced sPLA2-IIa protein expression and PGE2 formation. Accordingly, the IL-1β-induced sPLA2-IIa promoter activity was also reduced by CB2 receptor agonists. IL-1β-induced iNOS expression and subsequent NO formation were not influenced by CB2 recptor activation. Matching the results I obtained with CB1 receptor agonists on IL-1β-induced PGE2 formation, I could observe an increased cPLA2 protein and mRNA expression with a subsequent increase in IL-1β-induced PGE2 formation by GPR55 stimulation. Stimulation with THC, an unselective CB agonist, increased the IL-1β-induced sPLA2-IIa protein expression and subsequently led to an enhanced IL-1β-induced PGE2 formation. Subjecting the cells to higher THC concentrations surprisingly led to a reduction of the IL-1b-induced sPLA2-IIa protein expression and PGE2 formation. A possible explanation may be the differential expression of the three CB receptors. At low concentrations THC may predominantly activate CB1 and GPR55 and with increasing concentration CB2 receptors may also be activated, slightly reversing the enhancing effect. Moreover, I could show that the CB1 receptor stimulation mediated phosphorylation and hence the activation of ERK1/2 MAPK. Additionally to ERK1/2, there was also a phosphorylation and activation of NFkB observed by CB1 receptor stimulation. In my thesis I could show for the first time that PPARα was activated by IL-1β in rMC. The IL-1β-induced PPARα promoter activity was completely inhibited by addition of the CB2 receptor agonist, JWH015. These findings were confirmed by inhibition of the IL-1β-induced PGE2 formation by a PPARα antagonist (MK-886). In summary, I could show that activation of CB1 receptors in our system led to a worsening of an inflammatory condition, whereas activation of the CB2 receptors led to the complete opposite; namely a reduction of the inflammatory response by reducing the sPLA2-IIa expression and PGE2 formation. GPR55 activation did not display any alteration of inflammatory conditions, since the classical inflammatory pathway was not influenced.
The reggie protein family consists of two homologous members, reggie-1 and reggie-2, also termed flotillin-2 and flotillin-1, respectively, that are ubiquitously expressed and evolutionarily well conserved, suggesting an important but so far ill-defined function. In various cell types, both reggies have been found to be constitutively associated with lipid rafts by means of acylation modifications and oligomerization. Lipid rafts are glycosphingolipid- and cholesterol-rich membrane microdomains which have been implicated in several cellular processes including membrane transport and signal transduction through growth factor receptors. However, the molecular details of these processes are still poorly understood. With the observation that reggies colocalize with activated glycosylphosphatidylinositolanchored proteins (GPI-APs) and Fyn kinase in rafts, a role for these proteins in signaling events has been suggested. In agreement with that, we have previously shown that reggie-1 becomes multiply tyrosine phosphorylated by Src kinases in response to epidermal growth factor (EGF) stimulation, pointing to a function for reggie-1 in growth factor signaling. Furthermore, overexpression of reggie-1 enhances spreading on fibronectin substrate in a tyrosine-dependent manner, thus revealing a role for reggie-1 in regulation of actin cytoskeleton through growth factor receptors. Due to the similarity shared by reggie proteins at amino acid level and to their ability to form hetero-oligomeric complexes, the first aim of this study was to analyze the putative tyrosine phosphorylation of reggie-2 in growth factor stimulated cells. Similarly to reggie-1, reggie-2 was found to be multiply tyrosine phosphorylated by Src kinase and to exist in a molecular complex with Src, with the degree of co-immunoprecipitation dependent on the activity of Src. Recent studies from us have also shown that administration of EGF results in the endocytosis of reggie-1 from the plasma membrane into endosomes, which is in line with a proposed role for reggies in membrane trafficking processes. In order to characterize in detail the endocytic mechanism that mediates the uptake of reggie-1, the dependency of reggie-1 endocytosis on clathrin and dynamin was investigated by means of overexpressing a variant form of Eps15 or a dominant negative form of dynamin-2. In either case the translocation of reggie-1 into endosomes in response to EGF was not affected, and this, together with the results that reggie-1 colocalized with cholera toxin (CTX) but not with transferrin receptor (TfnR) during EGF signaling, indicates that reggie-1 is taken up by means of a dynaminindependent, raft-mediated pathway. These findings are very well in line with recent data showing the pathway of entry into cells of reggie-2 as a raft-mediated endocytic pathway. The endocytosis of reggie-2 in response to EGF was also analyzed in this study. Similarly to reggie-1, in growth factor stimulated cells reggie-2 underwent a translocation from the plasma membrane to endosomes where the two reggies were found to colocalize with each other, suggesting that epidermal growth factor signaling might trigger the endocytosis of reggie oligomers. In addition, colocalization with both the late endosomal marker LAMP3/CD63 and epidermal growth factor receptor (EGFR) was detected, again indicating a function for reggies in signal transduction through growth factor receptors. EGFR has been reported to localize in rafts but, although this association is thought to be functional during EGF stimulation, how segregation of EGFR into rafts modulates its endocytosis and signaling is still under debate. Since reggie oligomers have recently been suggested to define a raft subtype, a further aim of this study was to investigate whether the depletion of reggies by means of small interfering RNA could interfere with the signaling and the trafficking through EGFR. Knockdown of reggie-2 resulted in an altered tyrosine phosphorylation of EGFR in response to EGF, while the degree of ubiquitination was not affected. Less efficient phosphorylation of tyrosine residues, especially of those which are docking sites for Grb2 and Shc, led in turn to an impaired activation of p38 and ERK1/2 MAPKs. Depletion of reggie-2 did not affect the early trafficking of activated EGFRs, with receptors being endocytosed and delivered to late endosomes as efficiently as in control cells. This would be in line with the normal degree of ubiquitination observed for EGFR, as ubiquitin moieties have been proposed to represent sorting tags that ensure receptor endocytosis into early endosomes and its proper intracellular trafficking. On the contrary, after prolonged EGF stimulation, depletion of reggie-2 resulted in a decreased downregulation of both receptor-bound ligand and EGFR, and in their accumulation in intracellular vesicles, thus pointing to a role for reggie-2 in the degradative pathway. Taken all together, these data ndicate that the association of EGFR with reggie-microdomains is likely to be important for proper receptor trafficking and signaling.
Reggie-1 (flotillin-2) and reggie-2 (flotillin-1) are membrane microdomain proteins which are associated with the membrane by means of acylation. They influence different cellular signaling processes, such as neuronal, T-cell and insulin signaling. Upon stimulation of the EGF receptor, reggie-1 becomes phosphorylated and undergoes tyrosine 163 dependent translocation from the plasma membrane to endosomal compartments. In addition, reggie-1 was shown to influence actindependent processes. Reggie-2 has been demonstrated to affect caveolin- and clathrin-independent endocytosis. Both proteins form homo- and hetero-oligomers, but the function of these oligomers has remained elusive. Moreover, it has not been clarified if functions of reggie-1 are also influenced by reggie-2 and vice versa. The first aim of the study was to further investigate the interplay and the heterooligomerization of reggie proteins and their functional effects. Both reggie proteins were individually depleted by means of siRNA. In different siRNA systems and various cell lines, reggie-1 depleted cells showed reduced protein amounts of reggie-1 and reggie-2, but reggie-2 knock down cells still expressed reggie-1 protein. The decrease of reggie-2 in reggie-1 depleted cells was only detected at protein but not at mRNA level. Furthermore, reggie-2 expression could be rescued by expression of siRNA resistant wild type reggie-1-EGFP constructs, but not by the soluble myristoylation mutant G2A. This mutant was also not able to associate with endogenous reggie-1 or reggie-2, which demonstrates that membrane association of reggie-1 is necessary for hetero-oligomerization. In addition, fluorescence microscopy studies and membrane fractionations showed that correct localization of overexpressed reggie-2 was dependent on co-overexpressed reggie-1. Thus, hetero-oligomerization is crucial for membrane association of reggie-2 and for its protein stability or protein expression. Moreover, the binding of reggie-2 to reggie-1 required tyrosine 163 of reggie-1 which was previously shown to be important for endosomal translocation of reggie-1. Since reggie-2 was implicated to function in clathrin- and caveolin-independent endocytosis pathways, the effect of reggie-2 depletion on reggie-1 endocytosis was investigated. Indeed, reggie-1 was dependent on reggie-2 for endosomal localization and EGF-induced endocytosis. By FRET-FLIM analysis it could be shown that reggie heterooligomers are dynamic in size or conformation upon EGF stimulation. Thus, it can be concluded that reggie proteins are interdependent in different aspects, such as protein stability or expression, membrane association and subcellular localization. In addition, these results demonstrate that the hetero-oligomers are dynamic and reggie proteins influence each other in terms of function. A further aim was the characterization of reggie-1 and reggie-2 function in actindependent processes, where so far only reggie-1 was known to play a role. Depletion of either of the proteins reduced cell migration, cell spreading and the number of focal adhesions in steady state cells. Thus, also reggie-2 affects actin-dependent processes. Further investigation of the focal adhesions during cell spreading revealed that depletion of reggie-1 displayed different effects as compared to reggie-2 knock down. Reggie-1 depleted cells had elongated cell-matrix-adhesions and showed reduced activation of FAK and ERK2. On the other hand, depletion of reggie-2 resulted in a restricted localization of focal adhesion at the periphery of the cell and decreased ERK2 phosphorylation, but it did not affect FAK autophosphorylation. Hence, reggie proteins influence the regulation of cell-matrix-adhesions differently. A link between reggie proteins and focal adhesions is the actin cross-linking protein -actinin. The interaction of -actinin with reggie-1 could be verified by means of co-immunoprecipitations and FRET-FLIM analysis. Reggie-1 binds -actinin especially in membrane ruffles and in other locations where actin remodeling takes place. Moreover, -actinin showed a different localization pattern during cell spreading in reggie-1 depleted cells, as compared to the control cells. These results provide further insights into the function of both reggie proteins. Their interplay and hetero-oligomerization was shown to be crucial for their role in endocytosis. In addition, both reggie proteins influence actin-dependent processes and differentially affect focal adhesion regulation.
Reforming the African Public Sector: Retrospect and Prospectsis an in-depth and wide-ranging review of the available literature on African public sector reforms. It illustrates several differing country experiences to buttress the main observations and conclusions. It adopts a structural/institutional approach which underpins most of the reform efforts on the continent. To contextualize reform of the public sector and understand its processes, dynamics and intricacies, the book examines the state and state capacity building in Africa, especially when there can be no state without an efficient public sector. In addition, the book addresses a number of theories such as the new institutional economics, public choice and new public management, which have in one way or another influenced most of the initiatives implemented under public sector reform in Africa. There is also a survey of the three phases of public sector reform which have emerged and the balance sheet of reform strategies, namely, decentralization, privatization, deregulation, agencification, co-production and public-private partnerships. It concludes by identifying possible alternative approaches such as developing a vigorous public sector ethos and sustained capacity building to promote and enhance the renewal and reconstruction of the African public sector within the context of the New Partnerships for Africa's Development (NEPAD), good governance and the Millennium Development Goals (MDGs).
The content of this book will explain A For various reasons Europeans and Germans left their Homeland. B How they travelled in groups and individually. C How they landed in South Australia. D The Newcomers reception in a British colony. E The treatment they received in Australia. F What the Germans and Europeans achieved in Australia.
Rate effects on aerodynamics of intervocalic stops : evidence from real speech data and model data
(2008)
This paper is a first attempt towards a better understanding of the aerodynamic properties during speech production and their potential control. In recent years, studies on intraoral pressure in speech have been rather rare, and more studies concern the air flow development. However, the intraoral pressure is a crucial factor for analysing the production of various sounds.
In this paper, we focus on the intraoral pressure development during the production of intervocalic stops.
Two experimental methodologies are presented and confronted with each other: real speech data recorded for four German native speakers, and model data, obtained by a mechanical replica which allows reproducing the main physical mechanisms occurring during phonation. The two methods are presented and applied to a study on the influence of speech rate on aerodynamic properties.
Rare or threatened vascular plant species of Wollemi National Park, central eastern New South Wales
(2008)
Wollemi National Park (c. 32o 20’– 33o 30’S, 150o– 151oE), approximately 100 km north-west of Sydney, conserves over 500 000 ha of the Triassic sandstone environments of the Central Coast and Tablelands of New South Wales, and occupies approximately 25% of the Sydney Basin biogeographical region. 94 taxa of conservation significance have been recorded and Wollemi is recognised as an important reservoir of rare and uncommon plant taxa, conserving more than 20% of all listed threatened species for the Central Coast, Central Tablelands and Central Western Slopes botanical divisions. For a land area occupying only 0.05% of these divisions, Wollemi is of paramount importance in regional conservation. Surveys within Wollemi National Park over the last decade have recorded several new populations of significant vascular plant species, including some sizeable range extensions. This paper summarises the current status of all rare or threatened taxa, describes habitat and associated species for many of these and proposes IUCN (2001) codes for all, as well as suggesting revisions to current conservation risk codes for some species. For Wollemi National Park 37 species are currently listed as Endangered (15 species) or Vulnerable (22 species) under the New South Wales Threatened Species Conservation Act 1995. An additional 50 species are currently listed as nationally rare under the Briggs and Leigh (1996) classification, or have been suggested as such by various workers. Seven species are awaiting further taxonomic investigation, including Eucalyptus sp. ‘Howes Swamp Creek’ (Doherty 26), known from a single location within the park, and Pultenaea sp. (Olinda) from Dunns Swamp – both these species remain undescribed, but are listed as endangered species. After applying IUCN criteria to the 94 taxa, 2 are considered Critically Endangered; 11 are considered Endangered; 23 are considered Vulnerable; 3 are considered Near Threatened; 19 are considered Data Deficient; and 36 are considered of Least Concern. It is likely that additional highly restricted plant taxa await discovery in remote locations.
Questions on transitivity
(2008)
This handout (it isn’t a paper) presents phenomena and questions, rather than conclusions, related to the concept of transitivity. The idea is to return to these questions at the end of the Workshop to see if we can have a clearer consensus about the best general analysis of phenomena associated with transitivity. Section 2 presents alternative analyses of transitivity and questions about transitivity in three languages I have worked on. Section 3 discusses a few of the different conceptualisations of transitivity that might be relevant to our thinking about the questions related to these languages or that bring up further questions. Section 4 presents some general questions that might be asked of individual languages.
Quantitative approaches to linguistic variation in IRC : implications for qualitative research
(2008)
Qualitative analysis of code choice, code switching, and language style in Internet Relay Chat (IRC) can shed light on functional-pragmatic aspects of the use of different linguistic varieties. However, in a qualitative analysis, the status of varieties within a channel or for a single chatter can only be guessed at. Moreover, qualitative research on linguistic variation in IRC often fails to generalize its findings due to a restricted database or a restricted view of a database. This article introduces an approach that allows for embedding of qualitative research within a quantitative research design. The quantitative method presented here enables general statements to be made about the use of varieties or the usage of certain chatters in a chat channel. The approach is exemplified with data from Swiss IRC channels, in which Swiss German dialects and standard German are used side by side. A large corpus is analyzed for static and dynamic aspects of dialect share. It is argued that this quantitative approach can provide a background for qualitative analysis and facilitate the selection process of relevant data required for qualitative analysis.
Quantitative analysis of snoRNA association with pre-ribosomes and release of snR30 by Rok1 helicase
(2008)
In yeast, three small nucleolar RNAs (snoRNAs) are essential for the processing of pre-ribosomal RNA—U3, U14 and snR30—whereas 72 non-essential snoRNAs direct site-specific modification of pre-rRNA. We applied a quantitative screen for alterations in the pre-ribosome association to all 75 yeast snoRNAs in strains depleted of eight putative helicases implicated in 40S subunit synthesis. For the modification-guide snoRNAs, we found no clear evidence for the involvement of these helicases in the association or dissociation of pre-ribosomes. However, the DEAD box helicase Rok1 was required specifically for the release of snR30. Point mutations in motif I, but not in motif III, of the helicase domain of Rok1 impaired the release of snR30, but this was less marked than in strains depleted of Rok1, and resulted in a dominant-negative growth phenotype. Dissociation of U3 and U14 from pre-ribosomes is also dependent on helicases, suggesting that release of the essential snoRNAs might differ mechanistically from release of the modification-guide snoRNAs. Keywords: ribosome biogenesis; RNA helicase; snoRNA
The seasonality of transport and mixing of air into the lowermost stratosphere (LMS) is studied using distributions of mean age of air and a~mass balance approach, based on in-situ observations of SF6 and CO2 during the SPURT (Spurenstofftransport in der Tropopausenregion, trace gas transport in the tropopause region) aircraft campaigns. Combining the information of the mean age of air and the water vapour distributions we demonstrate that the tropospheric air transported into the LMS above the extratropical tropopause layer (ExTL) originates predominantly from the tropical tropopause layer (TTL). The concept of our mass balance is based on simultaneous measurements of the two passive tracers and the assumption that transport into the LMS can be described by age spectra which are superposition of two different modes. Based on this concept we conclude that the stratospheric influence on LMS composition is strongest in April with tropospheric fractions (α1) below 20% and that the strongest tropospheric signatures are found in October with (α1 greater than 80%. Beyond the fractions, our mass balance concept allows to calculate the associated transit times for transport of tropospheric air from the tropics into the LMS. The shortest transit times (<0.3 years) are derived for the summer, continuously increasing up to 0.8 years by the end of spring. These findings suggest that strong quasi-horizontal mixing across the weak subtropical jet from summer to mid of autumn and the considerably shorter residual transport time-scales within the lower branch of the Brewer-Dobson circulation in summer than in winter dominates the tropospheric influence in the LMS until the beginning of next year's summer.
Motivated by the prominent role of electronic limit order book (LOB) markets in today’s stock market environment, this paper provides the basis for understanding, reconstructing and adopting Hollifield, Miller, Sandas, and Slive’s (2006) (henceforth HMSS) methodology for estimating the gains from trade to the Xetra LOB market at the Frankfurt Stock Exchange (FSE) in order to evaluate its performance in this respect. Therefore this paper looks deeply into HMSS’s base model and provides a structured recipe for the planned implementation with Xetra LOB data. The contribution of this paper lies in the modification of HMSS’s methodology with respect to the particularities of the Xetra trading system that are not yet considered in HMSS’s base model. The necessary modifications, as expressed in terms of empirical caveats, are substantial to derive unbiased market efficiency measures for Xetra in the end.
Strong perturbations of the Arctic stratosphere during the winter 2002/2003 by planetary waves led to enhanced stretching and folding of the vortex. On two occasions the vortex in the lower stratosphere split into two secondary vortices that re-merged after some days. As a result of these strong disturbances the role of transport in and out of the vortex was stronger than usual. An advection and mixing simulation with the Chemical Lagrangian Model of the Stratosphere (CLaMS) utilising a suite of inert tracers tagging the original position of the air masses has been carried out. The results show a variety of synoptic and small scale features in the vicinity of the vortex boundary, especially long filaments peeling off the vortex edge and being slowly mixed into the mid latitude environment. The vortex folding events, followed by re-merging of different parts of the vortex led to strong filamentation of the vortex interior. During January, February, and March 2003 flights of the Russian high-altitude aircraft Geophysica were performed in order to probe the vortex, filaments and in one case the merging zone between the secondary vortices. Comparisons between CLaMS results and observations obtained from the Geophysica flights show in general good agreement. Several areas affected by both transport and strong mixing could be identified, allowing explanation of many of the structures observed during the flights. Furthermore, the CLaMS simulations allow for a quantification of the air mass exchange between mid latitudes and the vortex interior. The simulation suggests that after the formation of the vortex was completed, its interior remaind relatively undisturbed. Only during the two re-merging events were substantial amounts of extra-vortex air transported into the polar vortex. When in March the vortex starts weakening additional influence from lower latitudes becomes apparent in the model results. In the lower stratosphere export of vortex air leads only to a fraction of about 5% polar air in mid latitudes by the end of March. An upper limit for the contribution of ozone depleted vortex air on mid-latitude ozone loss is derived, indicating that the maximum final impact of dilution is on the order of 50%.
Purim and parodies
(2008)
The respiratory chain is composed of protein complexes residing in the inner mitochondrial membrane of eukaryotes or in the cytoplasmic membrane of prokaryotes. This cellular energy converter transforms a redox potential stored in low potential substrates into an electrochemical potential across the respective membrane. Typical respiratory chains contain the complexes I, II, III and IV named according to their sequence in the respiratory chain reaction. Electrons of low potential substrates enter at complex I or II and are passed via complex III to complex IV where they are transferred to oxygen. The transport of electrons between the complexes is mediated by small electron shuttles like quinol or cytochrome c. Two different models describe their exchange either by (1) random collision of freely diffusible electron shuttles and membrane protein complexes or (2) arrangement of the complexes in supercomplexes enabling direct channeling of electron shuttles. In the Gram positive bacterium Corynebacterium glutamicum, the complex III to complex IV electron shuttle cytochrome c is not diffusible but a covalently bound part of the diheme cytochrome subunit QcrC of complex III. Therefore, the complexes III and IV have to form a supercomplex for electron transduction. The aim of this thesis was to purify and characterise this obligatory supercomplex III/IV of C. glutamicum. To gain sufficient biomass of C. glutamicum as starting material for purification, a phosphate buffered minimal medium was developed that enabled yield of total 120 g wet cell mass (38 g dry mass) in 12 L (6×2 L) shaking cultures. The determined conversion factor of glucose into biomass was 0.46 g/g indicating an intact respiratory chain. The yield was increased by bioreactor cultivation to ~690 g wet cell mass (~220 g dry mass) in ~10 L culture volume. A previously described homologous expression system was applied that produces the complex IV subunit CtaD with a fused Strep-tag II to facilitate purification. Affinity purifications using the Strep-tag II affinity to Strep-Tactin resin yielded a mixture of complexes and supercomplexes. Two supercomplex III/IV versions named supercomplex A and B and free complex IV were identified in this mixture by size exclusion chromatography, redox difference spectroscopy and two dimensional polyacrylamide gel electrophoresis including blue native polyacrylamide electrophoresis. The here presented downscaled blue native polyacrylamide electrophoresis method with analysis times of ~1 h enabled efficient screening of factors influencing the stability of supercomplex III/IV. The screening resulted that the integrity of supercomplex III/IV is preserved by using neutral detergents at minimal detergent to protein ratios for solubilisation and low detergent concentrations for purification and storage slightly above the required critical micellar concentration. Furthermore, pH <=7.5 is required for stability of supercomplex III/IV. Large biomass yields enabled upscaling of supercomplex III/IV affinity purification. Application of the identified stability conditions resulted in affinity purified samples free of supercomplex B. The major component supercomplex A was efficiently separated from residual free complex IV by preparative size exclusion chromatography. Concentration of purified supercomplex A by ultracentrifugation resulted in integrity of the supercomplex for several days at 4 °C. Purified supercomplex A contains ten different previously described subunits. The heme content of supercomplex A relative to the protein mass is heme A: 6.0 μmol/g, heme B: 6.5 μmol/g, and heme C: 5.8 μmol/g determined by redox difference spectroscopy and biochemical protein quantification. This indicates an equimolar ratio of complex III and complex IV in supercomplex A. Supercomplex A has quinol oxidase activity that is inhibited by stigmatellin or sodium azide. The turnover number of transferred electrons per complex III monomer is 148 s−1 at 25° C. The homogeneity and stability of the prepared supercomplex A enabled the growth of threedimensional crystals of up to 0.1 mm in length. Their composition of supercomplex A was verified by redox difference spectroscopy of intact crystals and blue native polyacrylamide electrophoresis of dissolved crystals. The crystals diffracted X-rays corresponding to a resolution of ~10 Å. Electron microscopy of negative stained samples revealed the uniform shape of purified supercomplex A particles with dimensions of 22 × 9 nm in the view plane. Combined heme quantification, size determination, determined activity, symmetry considerations, and particle shape indicate that supercomplex A has a central dimer of complex III and two monomers of complex IV on opposite sides. This conformation is functionally reasonable because it provides each complex III monomer with one complex IV monomer as electron acceptor. Therefore, the stoichiometry of supercomplex A is most likely III2IV2. The sensitivity of supercomplex A to detergents indicated a role of phospholipids in its stability. Therefore, a method for phospholipid identification and quantification was developed that is suitable for detergent solubilised crude and purified membrane protein samples. The analysis combines separation of phospholipid classes according to their head group by normal phase high performance liquid chromatography with evaporative light scattering detection. Calibration with external standard allows quantification of phospholipid amount in the range of 0.25-12 μg. The method is verified by analysing the phospholipid content of the well characterised complex III of Saccharomyces cerevisiae. The reduction of its phospholipid content during its purification steps is monitored. The complex III sample purified to crystallisation quality contains the phospholipid content that was also observed in previously reported structures determined by X-ray crystallography. Purified stable supercomplex A from C. glutamicum revealed a large content of bound phospholipids. The main differences between intact supercomplex A and a mixture of potentially disintegrated smaller complexes is that intact supercomplex A has a doubled phosphatidic acid content and an increased phosphatidyl glycerol content. The importance of the small anionic phosphatidic acid for mediation of contacts between complexes in a supercomplex is discussed. The total phospholipid content of stable supercomplex A is sufficient for a complete belt surrounding the supercomplex in the membrane plane. This indicates that also all essential internal phospholipid binding positions are occupied and potentially stabilise supercomplex A.
The paper presents an additional argument for a specific account of semantic binding: the flat-binding analysis. The argument is based on observations concerning sloppy interpretations in verb phrase ellipsis when the binder is not the subject of the elided VP. In one such case, it is important that one of the binders belong to the domain of the other. This case can be derived from the flat-binding analysis as is shown in the paper, while it is unclear how to account for it within other analyses of semantic binding.
Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933
We present the results of an experimental study which targets prosodic correlates of subclausal quotation marks. We found that written sentences containing passages enclosed by quotation marks were read aloud in a manner that significantly differs in prosody from spoken realizations of corresponding disquoted counterparts. However, we also observed that such prosodic marking of subclausal quotation wasn't strong enough to survive subsequent back-translation into written language: there was no correlation between the presence/absence of quotation marks in the original written examples, and the presence/absence of quotation marks in corresponding back-translations from oral renditions. We investigated three different kinds of uses of quotation marks and found no systematic difference between them with respect to prosodic marking.
The Göttingen conference Systematics 2008 is the first joint meeting of the Gesellschaft für Biologische Systematik (GfBS) and the German Botanical Society, section Biodiversity and Evolutionary Biology (DBG), being the 10th Annual Meeting of the GfBS and the 18th International Symposium Biodiversity and Evolutionary Biology of the DBG. The conference programme covers biological systematics in the widest sense and provides ample opportunities for oral and poster presentations on new advances in plant, animal and microbial systematics. This volume brings together the abstracts of invited speaches from the plenary sessions on Progress in Deep Phylogeny, Speciation and Phylogeography, and New Trends in Biological Systematics as well as those of submitted talks and poster sessions.The Göttingen conference Systematics 2008 is the first joint meeting of the Gesellschaft für Biologische Systematik (GfBp. and the German Botanical Society, section Biodiversity and Evolutionary Biology (DBG), being the 10th Annual Meeting of the GfBS and the 18th International Symposium Biodiversity and Evolutionary Biology of the DBG. The conference programme covers biological systematics in the widest sense and provides ample opportunities for oral and poster presentations on new advances in plant, animal and microbial systematics. This volume brings together the abstracts of invited speaches from the plenary sessions on Progress in Deep Phylogeny, Speciation and Phylogeography, and New Trends in Biological Systematics as well as those of submitted talks and poster sessions.
We investigate the implications of the r-modes instability on the composition of a compact star rotating at a sub-millisecond period. In particular, the only viable astrophysical scenario for such an object, wich might present inside the Low Mass X-ray Binary associated with the x-ray transient XTE J1739-285, is that it has a strangeness content. Since previous analysis indicate that hyperonic stars or stars containing a kaon condensate are unlikely because of the mass-shedding constraint, the only remaining possibility is that such an object is either a strange quark star or a hybrid quark-hadron star.
We find and describe four futures markets where the bid-ask spread is bid down to the fixed price tick size practically all the time, and which match counterparties using a pro-rata rule. These four markets´ offered depths at the quotes on average exceed mean market order size by two orders of magnitude, and their order cancellation rates (the probability of any given offered lot being cancelled) are significantly over 96 per cent. We develop a simple theoretical model to ex- plain these facts, where strategic complementarities in the choice of limit order size cause traders to risk overtrading by submitting over-sized limit orders, most of which they expect to cancel.
Bayesian learning provides the core concept of processing noisy information. In standard Bayesian frameworks, assessing the price impact of information requires perfect knowledge of news’ precision. In practice, however, precision is rarely dis- closed. Therefore, we extend standard Bayesian learning, suggesting traders infer news’ precision from magnitudes of surprises and from external sources. We show that interactions of the different precision signals may result in highly nonlinear price responses. Empirical tests based on intra-day T-bond futures price reactions to employment releases confirm the model’s predictions and show that the effects are statistically and economically significant.
Preliminary Checklist of the Mecoptera of Florida: Earwigflies, Hangingflies, and Scorpionflies
(2008)
We provide the first species checklist of Mecoptera indigenous to Florida, based upon preliminary data gathered primarily from specimens housed in the Florida State Collection of Arthropods. There are 11 described and one undescribed species of mecopterans, representing three families, inhabiting the state of Florida. These include the recently discovered meropeid (earwigfly), Merope tuber Newman, four species of bittacids (hangingflies), represented by the genus Bittacus Latreille, and 7 species (one undescribed) of panorpids (scorpionflies), represented by the genus Panorpa Linnaeus. We are not certain if one of these, Bittacus texanus Banks, is indigenous, represents a nonindigenous occurrence, or is simply erroneous. Two of the species on our list, Bittacus stigmaterus Say and Panorpa venosa Westwood, represent first state records and one species, Panorpa floridana Byers, is endemic. Six of the species which have been recorded in Florida, M. tuber, Bittacus punctiger Westwood, Panorpa rufa Gray, Panorpa pachymera Byers, Panorpa lugubris Swederus and P. venosa, represent the southernmost records for these species in the continental United States. Perceived diversity and abundance of mecopteran species in Florida are limited by climate, biogeography, and collection bias.
Exported proteases of Helicobacter pylori (H. pylori) are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI). Among these, we found the predicted serine protease HtrA (Hp1019), which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.
Precipice
(2008)
Madam Essin stood watching the young people holding each other. She looked at the young man who was her son. How handsome he looked. When he smiled he had that elusive curve on his lips that reminded her of her husband. She had been unable to resist that curve of the lips even after eight years of marriage. When her husband smiled she had the feeling he was looking down on her in amused condescension. This used to annoy her but she could not resist the charm he exuded. Now here she was an abandoned wife with an estranged son. Her thoughts roved as she watched them, plunging into the past, the present and the future. The girl brought back the past. She wished she could obliterate that past from her life and her son's. In Precipice, Susan Nkwentie Nde, in her first novel, has a way of weaving past intrigues and present emotions to keep all guessing about what will be. She opens up her characters for the reader to enter and inhabit their minds and bodies in a compelling story of love and estrangement, happy accidents, quest and survival.
The following essay in comparative literature focuses on three comedies that perhaps satisfy the aforementioned conditions, namely Ludvig Holberg's 'Mascarade' of 1724, Carlo Goldoni's 'I Rusteghi' of 1760, and Georg Büchner's 'Leonce und Lena' of 1836. My interest is typological, not genealogical, i.e. I do not claim that the later authors knew the earlier dramas; for the three authors belong to different cultures and write their texts in different languages - Danish, Venetian, and German. Still, even if am not interested in the question, I cannot exclude such knowledge either. There are similarities not only in the main structure, but also in the details; and Holberg is possibly known to Goldoni and certainly to Büchner.
Disruption of the complex gastrointestinal ecosystem between the resident microflora and the colonic epithelial cells has been associated with increased inflammation and altered cell growth. Possible endpoints of this disturbance are IBD and CRC. The data presented in this thesis, entitled "PPARgamma as molecular target of epithelial functions in the gastrointestinal tract", shed further light on the underlying molecular mechanisms contributing to the well ordered homeostasis of this gastrointestinal ecosystem. Except for elucidating important roles for mesalazine and the dietary HDAC inhibitors butyrate and SFN in a) the modulation of cellular growth, b) the induction of APs, and c) the control of NFkappaB signalling in CRC cells, the involvement of the nuclear hormone receptors PPARgamma und VDR as "gatekeepers" in these intricate regulatory mechanisms were established. Future work will be engaged in analysing whether these in vitro findings are also physiologically relevant in regard to prevention and therapy of gastrointestinal diseases. Within the scope of this work, in Paper I and II it could be demonstrated that butyrate and mesalazine act via PPARgamma to induce their anti-proliferative and pro-apoptotic actions along the caspase signalling pathway. Activation of the intrinsic and extrinsic signalling trail and the down-regulation of anti-apoptotic proteins are responsible for increased caspase-3 activity caused by butyrate. In contrast, mesalazine merely activates this cascade via the extrinsic trail and the IAPs. Moreover, a signal transduction pathway leading to increased cell death via p38 MAPK - PPARgamma - caspase-3 in response to butyrate was unveiled. In addition, there is strong evidence that mesalazine-mediated pro-apoptotic and growth-inhibitory abilities are controlled by PPARgamma-dependent and -independent mechanisms which appear to be triggered at least in part by the modulation of the tumor suppressor gene PTEN and the oncoprotein c-myc, respectively. In Paper III and IV the induction of the APs HBD-2 and LL-37 in response to the dietary HDAC inhibitors butyrate and SFN was pinpointed. Regarding the molecular events of this regulation, the data presented in this thesis provide strong evidence for the involvement of VDR in HBD-2- and LL-37-induced gene expression, while the participation of PPARgamma was excluded. Moreover, the role for p38 MAPK and TGF-beta1 in the up-regulation of LL-37 caused by butyrate was established. In contrast, SFN-mediated induction of HBD-2 is modulated via ERK1/2 signalling. The findings in Paper V clearly refer to the involvement of the nuclear hormone receptors PPARgamma and VDR in butyrate-mediated suppression of inducible NFkappaB activation dependent on the stimulated signalling pathway caused by LPS or TNFalpha. Moreover, an inhibitory role for VDR in the regulation of basal NFkappaB activation was revealed. On the contrary, a modulating role for PPARgamma on basal NFkappaB could be debarred. Altogether the data presented in this thesis not only provide new insights in the understanding of the fundamental gastrointestinal physiology regulated by nuclear hormone receptors, but also may offer opportunities for the development of potential drug targets and therapeutic strategies in the treatment of IBD and CRC.
In this paper we compare the distribution of PPs introducing external arguments in nominalizations with PPs introducing external arguments in the verbal domain. We show that several mismatches exist between the behavior of PPs in nominalizations and PPs in the verbal domain. This leads us to suggest that while PPs in the verbal domain are licensed by functional structure alone, within the nominal domain, PPs can also be licensed via an interplay of the encyclopaedic meaning of the root involved and the properties of the preposition itself. This second mechanism kicks in in the absence of functional structure.
Macrozamia johnsonii D. Jones & K. Hill is a locally endemic cycad (family Zamiaceae) with a restricted occurrence in north-eastern New South Wales and currently listed as Endangered. Based on recent field surveys, its mean population size is estimated as approximately 3.5 million mature plants, with the lower bound of the 95% confidence interval at 1.9 million mature plants. Thirty percent of the population occurs in a formal reserve. Macrozamia johnsonii occurs in grassy eucalypt forest, shrubby wet sclerophyll forest and in rainforest. It occurs most frequently on steeply sloping sites with high moisture index. There are no immediate significant threats to the species although timber harvesting is judged to be a potential longer term threat to part of the population. The conservation status of Macrozamia johnsonii is assessed using IUCN criteria and thresholds, using population size and extent data from this study and a plausible range of values based on available circumstantial evidence for parameters for which quantitative estimates are not available. Based on this assessment, we regard the conservation status of Macrozamia johnsonii to be in the category of Least Concern, and that its current listing as an Endangered species under the NSW Threatened Species Conservation Act (1995) needs to be revised.
The orchid genus Epipactis is represented by 25 species in Europe (Richards 1982). Epipactis helleborine (L.) Crantz is the most common and widely distributed species of the genus (Wiefelspütz 1970), and is a prime example for wasp-flowers, because it is mainly pollinated by social wasps (Hymenoptera: Vespidae), like Vespula vulgaris and V. germanica (Müller 1873). Darwin (1888) already noticed that E. helleborine is almost exclusively ignored by bees and bumblebees, an observation that was confirmed in recent investigations (Keppert 2001). The flowers of E. helleborine show morphological, physiological and phenological adaptations to the visit and the pollination by Vespidae (Keppert 2001). They possess a reddish-brown or dirty purple coloration of the inflorescence (Keppert 2001), have relatively small, mostly bulbous blossoms with a broad entrance and bulbous widened, nectar-rich juice holders (Müller 1873, 1881; Schremmer 1962). Although there is much reported about wasp-pollinated flowers there is little known about the signals that are responsible for the attraction of wasps. Wiefelspütz (1970) proclaimed the statement that only the visual stimulus is responsible for the wasp attraction. Recently studies, however, assumed that odour is involved in the wasp attraction (Keppert 2001). Hölzler (2003) showed that the main attraction of the wasp-flower Epipactis for pollinators is its olfactory stimulus. It remains an unanswered question why E. helleborine flowers almost exclusively attracts social wasps, as opposed to bees and bumblebees. In this study we analysed the role of floral volatiles which are responsible for the specific attraction of social wasps. We supposed a mimicry-system in E. helleborine for the specific attraction of pollinators for the following reasons. So-called “green leaf volatiles” (GLVs) are emitted by plants while herbivorous insects, for example caterpillars, feed on them. GLVs thereby attract predators or parasitoids of the herbivorous insects (Dicke & Sabelis 1988; Turlings & al. 1990, 1995; Dicke & Vet 1999). Among the GLVs so far identified in former studies there are aldehydes, compounds that were also found in flower extracts of E. helleborine (Hölzler 2003). Therefore, we postulated that E. helleborine flowers produce GLVs in order to attract prey hunting social wasps for pollination. We performed bioassays and analysed flower odour gained to headspace-sampling using gas chromatography (GC), mass spectrometry (GC-MS) and gas chromatography coupled with electrophysiological analysis (GC-EAD) to investigate the hypothesis that E. helleborine flowers mimic “green leaf volatiles” (GLVs) to attract their pollinators.
Many older US households have done little or no planning for retirement, and there is a substantial population that seems to undersave for retirement. Of particular concern is the relative position of older women, who are more vulnerable to old-age poverty due to their longer longevity. This paper uses data from a special module we devised on planning and financial literacy in the 2004 Health and Retirement Study. It shows that women display much lower levels of financial literacy than the older population as a whole. In addition, women who are less financially literate are also less likely to plan for retirement and be successful planners. These findings have important implications for policy and for programs aimed at fostering financial security at older ages.
This study provides a species-level phylogeny for the Neotropical brassoline genus Eryphanis Boisduval based on 43 morphological characters. A revised generic definition is given. Three subspecies are elevated to species status and a new species is described; E. bubocula (Butler, 1872), status revised; E. lycomedon (C. Felder and R. Felder, 1862), status revised; E. opimus (Staudinger, 1887), status revised; and E. greeneyi Penz and DeVries, new species. Diagnoses, annotated redescriptions, and illustrations of habitus and genitalia are provided for the nine Eryphanis species.
In the present work, the photo-protection mechanisms in plants and purple bacteria were investigated experimentally at the molecular level. For this purpose, several spectroscopic methods were combined and applied to elucidate the function of carotenoids, pigments of the photosynthetic apparatus, in photo-protection. The experiments were focused on the mechanisms involved in quenching of singlet and triplet states of the electronically excited (bacterio)chlorophylls. This photosynthetic reaction events occur on an ultrafast time-scale. Measuring such short-lived events, and understanding the underlying principles, demand some of the most precise experiments and exact measurement technologies currently available. This implies certain requirements for the light source used: a suitable wavelength within the absorption band of the sample, sufficient power, and, most importantly, a pulse duration short compared to the studied reaction. Nowadays, we can achieve all this requirements using femtosecond-spectroscopic systems, which produce laser pulses shorter than 100 femtoseconds (fs). Transient absorption spectroscopy provides important information on molecular dynamics interrogating electronic transitions. The technique is based on photochemical generation of transient species with femtoseconds pump pulses and measuring transient absorption changes of the sample using a second, time delayed probe pulse which in this case is a spectrally broad white-light pulse.
Chloroplast function depends on the translocation of cytosolically synthesized precursor proteins into the organelle. The recognition and transfer of most precursor proteins across the outer membrane depend on a membrane inserted complex. Two receptor components of this complex, Toc34 and Toc159, are GTPases, which can be phosphorylated by kinases present in the hosting membrane. However, the physiological function of phosphorylation is not yet understood in detail. It is demonstrated that both receptors are phosphorylated within their G-domains. In vitro, the phosphorylation of Toc34 disrupts both homo- and heterodimerization of the G-domains as determined using a phospho-mimicking mutant. In endogenous membranes this mutation or phosphorylation of the wild-type receptor disturbs the association of Toc34, but not of Toc159 with the translocation pore. Therefore, phosphorylation serves as an inhibitor for the association of Toc34 with other components of the complex and phosphorylation can now be discussed as a mechanism to exchange different isoforms of Toc34 within this ensemble.
Background: Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs) emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results: We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of "chromaffin" granules were significantly increased. Conclusions: BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.
The following paper is about artists doing experimental and performative art who expect the spectators to become participants in the process of artwork production. The artwork is thus produced through a process of participation. As a researcher, I was similarly expected to participate in the artwork process. As I observed, the artists worked at having their agency in the artwork process recognized by the participating spectators. At the same time, the artists create a certain proximity to the spectators-participants through performing art, which I call "performing proximity." By involving the participants in their art-in-process, they make use of their agency to redefine the artworld and enlarge it into other social worlds. I also discuss how artists' ability to enact redefined social worlds can be compared to agency in performative social science and in biographical research.
Conclusion Scale Integration Based on the results of spike-field coherence, the underlying process of shortterm memory seems to involve networks of different sizes within and, most probably, beyond prefrontal cortex. Spikes, which were generated by single neurons, cooperate with local field potentials, which were the slower fluctuations of the environment. Although differences among behavioral conditions appear to be based on rather few instances of phase-locked spikes, the task-related effects on spike-field coherence are highly reliable and cannot be explained by chance, as the comparison of results from experimental and simulated data shows. The differential locking of prefrontal neuron populations with two different frequency bands in their input signals suggests that neuronal activity underlying short-term memory in prefrontal cortex transiently engages cortical circuits on different spatial scales, probably in order to coordinate distributed processes. NeuroXidence method and Synchronizedfiring Based on the results of the calibration datasets, for bi- and multi-variate cases, the extension of NeuroXidence remains its sensitivity and reliability of detecting coordinate firing events for different processes. Based on this extension of NeuroXidence, we demonstrated that in monkey’s prefrontal cortex during short-term memory task, encoding and maintenance of the information rely on the formation of neuronal assemblies characterized by precise and reliable synchronization of spiking activity on a millisecond time scale, which is consistent with the results from spike-spike coherence. The task and performance dependent modulation of synchrony reflects the dynamic formation of group of neurons has large effect on short-term-memory.
The lysosomal ABC transporter associated with antigen processing-like (TAPL, ABCB9) acts as an ATP-dependent polypeptide transporter with broad length selectivity. To characterize in detail its substrate specificity, a procedure for functional reconstitution of human TAPL was developed. By intensive screening of detergents, ideal solubilization conditions were evolved with respect to efficiency, long term stability, and functionality of TAPL. TAPL was isolated in a two-step procedure with high purity and, subsequently, reconstituted into proteoliposomes. The peptide transport activity of reconstituted TAPL strongly depends on the lipid composition. With the help of combinatorial peptide libraries, the key positions of the peptides were localized to the N- and C-terminal residues with respect to peptide transport. At both ends, TAPL favors positively charged, aromatic, or hydrophobic residues and disfavors negatively charged residues as well as asparagine and methionine. Besides specific interactions of both terminal residues, electrostatic interactions are important, since peptides with positive net charge are more efficiently transported than negatively charged ones.
The deposition of the amyloid β-protein (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD). Aβ-deposits show the morphology of senile plaques and cerebral amyloid angiopathy (CAA). Senile plaques and vascular Aβ-deposits occur first in neocorti-cal areas. Then, they expand hierarchically into further brain regions. The distribution of Aβ plaques throughout the entire brain, thereby correlates with the clinical status of the patients. Imaging techniques for Aβ make use of the hierarchical distribution of Aβ to distinguish AD patients from non-AD patients. However, pathology seen in AD patients represents a late stage of a pathological process starting 10–30 years earlier in cognitively normal individuals. In addition to the fibrillar amyloid of senile plaques, oligomeric and monomeric Aβ is found in the brain. Recent studies revealed that oligomeric Aβ is presumably the most toxic Aβ-aggregate, which interacts with glutamatergic synapses. In doing so, dendrites are presumed to be the primary target for Aβ-toxicity. In addition, vascular Aβ-deposits can lead to capillary occlusion and blood flow disturbances presumably contributing to the alteration of neurons in addition to the direct neurotoxic effects of Aβ. All these findings point to an important role of Aβ and its aggregates in the neurodegenerative process of AD. Since there is already significant neuron loss in AD patients, treatment strategies aimed at reducing the amyloid load will presumably not cure the symptoms of dementia but they may stop disease progression. Therefore, it seems to be necessary to protect the brain from Aβ-toxicity already in stages of the disease with minor neuron loss before the onset of cognitive symptoms.
The Pan-Africanist debate is back on the historical agenda. The stresses and strains in the union of Tanganyika and Zanzibar since its formation some forty years ago are not showing any sign of abating. Meanwhile, imperialism under new forms and labels continues to bedevil the continent in ever-aggressive, if subtle, ways. The political federation of East Africa, which was one of the main spin-offs of the Pan-Africanism of the nationalist period, is reappearing on the political stage, albeit in a distorted form of regional integration. It is in this context that the present study is situated. Backgrounding the major dramas of the union of Tanganyika and Zanzibar this book studies the personalities involved and their politics, and includes an account of the Dodoma CCM conference that toppled President Jumbe. It is also a detailed legal analysis of the union incorporating powerful new material.
Transcriptional activation involves the ordered recruitment of coactivators via direct interactions between distinct binding domains and recognition motifs. The p160/SRC/NCoA coactivator family comprises three members (NCoA-1, -2 and -3), which are organized in multiprotein coactivator complexes. We had identified the PAS-B domain of NCoA-1 as an LXXLL motif binding domain. Here we show that NCoA family members are able to interact with other full-length NCoA proteins via their PAS-B domain and they specifically interact with the CBP-interaction domain (CID/AD1) of NCoA-1. Peptide competition, binding experiments and mutagenesis of LXXLL motifs point at distinct binding motif specificities of the NCoA PAS-B domains. NMR studies of different NCoA-1-PAS-B/LXXLL peptide complexes revealed similar although not identical binding sites for the CID/AD1 and STAT6 transactivation domain LXXLL motifs. In mechanistic studies, we found that overexpression of the PAS-B domain is able to disturb the binding of NCoA-1 to CBP in cells and that a CID/AD1 peptide competes with STAT6 for NCoA-1 in vitro. Moreover, the expression of an endogenous androgen receptor target gene is affected by the overexpression of the NCoA-1 or NCoA-3 PAS-B domains. Our study discloses a new, complementary mechanism for the current model of coactivator recruitment to target gene promoters.
Life-threatening fungal infections are becoming increasingly common for immunocompromised patients such as those with AIDS, or those undergoing organ transplantation or chemotheraphy, as well as for other health-vulnerable patients. Excellent targets for antifungal drugs are chitin synthases, which are essential for survival of the fungus and lacking in humans. To design new antifungal drugs, knowledge of the three-dimensional structure and mechanism of action of chitin synthases are crucial. Chitin synthases are members of an important family of enzymes that synthesize structural polysaccharides, such as cellulose, β(1,3)-glucan, β(1,4)-mannan and hyaluronan. Therefore, chitin synthases could be used as a model system to understand these more complex enzymes, which are also of major medical and commercial importance. Chitin synthase 2 from Saccharomyces cerevisiae (ScChS2), the protein under study, is an integral membrane protein that synthesizes the primary septum between mother and daughter cells in budding yeast. It is essential for proper cell separation and expected to be highly regulated. An important aspect is that ScChS2 shows 55% sequence identity and is functionally analogous to chitin synthase 1 from the human opportunistic pathogen Candida albicans, this enzyme is also essential for cell survival (Munro, Winter et al. 2001). ...
Out of the Wreckage
(2008)
Background Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries. Methods Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques. Results Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed. Conclusion The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Background The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. Methods A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Gottinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Results Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. Conclusion The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.
The origins of the Cuban bee fauna are reviewed. This fauna began to form 40 million years ago during the Proto Antilles period, through ancestors that arrived in successive invasions from adjacent continental areas. The composition of the Antillean fauna has evolved continuously over millions of years until the present time. The native bee fauna of Cuba is represented by 89 species, contained in 29 genera and 4 families. The number of genera represented per family is as follows: Colletidae (3), Halictidae (8), Megachilidae (4), and Apidae (14). The Cuban apifauna contains four principal groups with distinct biogeographic histories: endemic species of Cuba (43.8%); endemic species of the Antilles shared among multiple islands (33.1%); continental species whose distribution includes the Antilles (16.8%); and species introduced through human activity (6.3%). An analysis of the distributions of Cuban bee species reveals that areas of highest species endemism coincide with the main mountainous nuclei of the East, Center and West. These were: the Sierra Maestra mountain range (with 25 species), Nipe-Sagua-Baracoa (15), the Mountain range of Guaniguanico (14) and the Massif of Guamuaya (14). The distribution of the bees in the Cuban Archipelago was not uniform, possibly due to the ecological conditions of the respective habitats, the diversity and presence of specific food plants, and interspecific competition. The endemism of bees in Greater Antilles is considered high keeping in mind the mobility of the group, as observed not only in Cuba (43.8%) but also Jamaica (50%), Hispaniola (45.6%), and in Puerto Rico and adjacent islands (26.5 %).
The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor {kappa}B activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
The purpose of this study was to reconstruct the depositional environment, the genesis and the composition of Miocene coals in the Kutai Basin, East Kalimantan, Indonesia and to improve our understanding of the factors controlling the organic and inorganic composition, variation of biomarkers, and the peat forming vegetation of the coals. To achieve the aim methods belonging to three different disciplines were applied: 1. Coal petrology (chapter 3) 2. Inorganic geochemistry: sulfur, pyrite and mineral matter distributions (chapter 4) 3. Organic geochemistry of saturated, aromatic hydrocarbon fractions and stable carbon isotopic composition (chapter 5 and 6) Coal petrology Coal developes from peat deposited in mires, mainly in swamps and raised bogs. It is therefore necessary to consider how peat was formed in the past. Coal contains a variety of plant tissues in different degrees of preservation. Tissues of distinct origin are microscopically identifiable and can frequently be related to certain parts of the plant, such as cuticles, woody structures, spores, algal, resin, etc. Together with the particles of less certain origin they are termed macerals which are the petrographic components of coal. During and after deposition of plant remains in sedimentary basins, the organic matter will undergo a sequence of physical, biochemical and chemical changes, which finally results in the formation of coals of increasing rank depending mainly on the temperature influence. The process of coalification begins with practically unaltered plant material and peat, and continues with increasing rank through brown coal, bituminous coal, and finally to anthracite as well as graphite. Coal petrography provides valuable of data of maceral and mineral percentages with reflectance values, which can be used to reconstruct the depositional environment and the coalification processes. In lower rank coals, the material is represented by a group of macerals called huminite, and in bituminous and anthracite coals by a group of macerals called vitrinite. Coal petrography analyses have been carried out on samples from some Miocene coal seams from Kutai Basin. The study has shown that huminite reflectance values of coal samples from ...
The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling. Keywords: Acute Myeloid Leukemia (AML), Allogeneic Stem Cell Transplantation (SCT), Indication, Cytogenetics, Polymerase Chain Reaction (PCR)
We document significant and robust empirical relationships in cross-country panel data between government size or social expenditure on the one hand, and trade and financial development indicators on the other. Across countries, deeper economic integration is associated with more intense government redistribution, but more developed financial markets weaken that relationship. Over time, controlling for country-specific effects, public social expenditure appears to be eroded by globalization trends where financial market development can more easily substitute for it.
Poster presentation: Background In the past years, once-daily (QD) dosing of antiretroviral combination therapy has become an increasingly available treatment option for HIV-1+ patients. Methods Open label study in which HIV-1+ patients treated with SAQ/RTV (1000/100 mg BID) and two NRTIs with HIV-RNA-PCR < 50 copies/ml were switched to SAQ/RTV(2000/100 mg QD) with unchanged NRTI-backbone. CD4-cells, HIV-RNA-PCR, SAQ and RTV drug-levels and metabolic parameters were compared. Summary of results 17 patients (15 male, 42 years), median CD4 456 ± 139/micro l were included so far. The median follow-up time is 4 months. The HIV-RNA-PCR remained <50 copies/ml for all patients. Fasting metabolic parameters remained unchanged. The SAQ AUC 0–12 h were significantly higher when given QD vs. BID (median 29,400 vs. 18,500 ng*h/ml; p = 0.009), whereas the Cmin, Cmax and AUC was lower for RTV when given QD vs. BID (7,400 vs. 11,700 ng*h/ml; p = 0.02). Conclusion In this ongoing study SAQ/RTV (2000/100 mg QD) was well tolerated and demonstrated higher SAQ and lower RTV drug levels as compared to the BID dosing schedule. (Table 1 and Figure 1.)
German linking elements are sometimes classified as inflectional affixes, sometimes as derivational affixes, and in any case as morphological units with at least seven realisations (e.g. -s-, -es-, -(e)n-, -e-). This article seeks to show that linking elements are hybrid elements situated between morphology and phonology. On the one hand, they have a clear morphological status since they occur only within compounds (and before a very small set of suffixes) and support the listener in decoding them. On the other hand, they also have to be analysed on the phonological level, as will be shown in this article. Thus, they are marginal morphological units on the pathway to phonology (including prosodics). Although some alloforms can sometimes be considered former inflectional endings and in some cases even continue to demonstrate some inflectional behaviour (such as relatedness to gender and inflection class), they are on their way to becoming markers of ill-formed phonological words. In fact, linking elements, above all the linking -s-, which is extremely productive, help the listener decode compounds containing a bad phonological word as their first constituent, such as Geburt+s+tag ‘birthday’ or Religion+s+unterricht ‘religious education’. By marking the end of a first constituent that differs from an unmarked monopedal phonological word, the linking element aids the listener in correctly decoding and analysing the compound. German compounds are known for their length and complexity, both of which have increased over time—along with the occurrence of linking elements, especially -s-. Thus, a profound instance of language change can be observed in contemporary German, one indicating its typological shift from syllable language to word language.
Much of the recent philosophical literature about distributive justice and equality in the domestic context has been dominated by a family of theories now often called ‘luck egalitarianism’, according to which it is unfair if some people are worse off than others through no choice or fault of their own. This principle has also found its way into the literature about global justice. This paper explores some difficulties that this principle faces: it is largely insensitive to the causes of global inequality, and it is so demanding that it can only give rise to weak moral claims. I go on to argue that a) understanding justice claims as merely weak claims rests on an implausible and impractical concept of justice, and b) using the global luck egalitarian argument in practical discourse is likely to lead to misunderstanding, and to be counterproductive if the aim is to tackle global inequality. While these considerations do not suffice to make a conclusive case against the luck egalitarian principle, they should be acknowledged by global luck egalitarians – as some similar problems have indeed been by domestic luck egalitarians – and need to be addressed.
Precursor protein translocation across the outer chloroplast membrane depends on the action of the Toc complex, containing GTPases as recognizing receptor components. The G domains of the GTPases are known to dimerize. In the dimeric conformation an arginine contacts the phosphate moieties of bound nucleotide in trans. Kinetic studies suggested that the arginine in itself does not act as an arginine finger of a reciprocal GTPase-activating protein (GAP). Here we investigate the specific function of the residue in two GTPase homologues. Arginine to alanine replacement variants have significantly reduced affinities for dimerization compared with wild-type GTPases. The amino acid exchange does not impact on the overall fold and nucleotide binding, as seen in the monomeric x-ray crystallographic structure of the Arabidopsis Toc33 arginine-alanine replacement variant at 2.0A. We probed the catalytic center with the transition state analogue GDP/AlF(x) using NMR and analytical ultracentrifugation. AlF(x) binding depends on the arginine, suggesting the residue can play a role in catalysis despite the non-GAP nature of the homodimer. Two non-exclusive functional models are discussed: 1) the coGAP hypothesis, in which an additional factor activates the GTPase in homodimeric form; and 2) the switch hypothesis, in which a protein, presumably the large Toc159 GTPase, exchanges with one of the homodimeric subunits, leading to activation.
In the late seventies, Bernard Comrie was one of the first linguists to explore the effects of the referential hierarchy (RH) on the distribution of grammatical relations (GRs). The referential hierarchy is also known in the literature as the animacy, empathy or indexibability hierarchy and ranks speech act participants (i.e. first and second person) above third persons, animates above inanimates, or more topical referents above less topical referents. Depending on the language, the hierarchy is sometimes extended by analogy to rankings of possessors above possessees, singulars above plurals, or other notions. In his 1981 textbook, Comrie analyzed RH effects as explaining (a) differential case (or adposition) marking of transitive subject ("A") noun phrases in low RH positions (e.g. inanimate or third person) and of object ("P") noun phrases in high RH positions (e.g. animate or first or second person), and (b) hierarchical verb agreement coupled with a direct vs. inverse distinction, as in Algonquian (Comrie 1981: Chapter 6).
The research presented in this thesis characterizes U2AF homology motifs (UHM) and their interactions with UHM ligand motifs (ULM) in the context of splicing regulation. UHM domains are a subgroup of RNA recognition motifs (RRM) originally discovered in the proteins U2AF65 and U2AF35. Whereas canonical RRMs are usually involved in binding of RNA, UHM domains bind tryptophan containing linear protein motifs (ULM) instead. In the first article, we analyze the complex network of interactions between splicing factors and RNA that initiate the assembly of the spliceosome at the 3´ splice site of an intron. The protein U2AF65 binds a pyrimidine-rich element in introns and recruits U2snRNP by binding its protein component SF3b155. My contribution was to define the binding site of the protein U2AF65 to the intrinsically unstructured N-terminus of the scaffolding protein SF3b155. I could show that the UHM domain of U2AF65 recognizes a ULM in SF3b155, and that this binding site is not overlapping with the binding sites of other splicing factors, like p14, to SF3b155. As the U2AF65-UHM:SF3b155-ULM interaction is mutually exclusive with an interaction between U2AF65-UHM and a ULM in the splicing factor SF1, which was reported to initially recognize the branch point sequence, my results provide the molecular details on how SF3b155 replaces SF1 during spliceosomal reorganizations. In the second article, we show that overexpression of the UHM domain of the splicing factor SPF45 induces exon 6 skipping in the pre-mRNA of Fas (CD95/APO-1). I provide evidence for in vitro binding of SPF45-UHM to ULM sequences in the splicing factors U2AF65, SF1, and SF3b155. I crystallized free and SF3b155-bound SPF45 UHM and solved both structures by X-ray crystallography. The analysis of the complex interface and sequence differences in the ULMs allowed me to design mutations of SPF45-UHM, which selectively inhibit binding to distinct ULMs. After assessing the ULM binding properties in vitro, we could show that the activity of SPF45-UHM in influencing the splicing pattern of Fas relies on interactions with SF3b155 and/or SF1, but that an interaction with U2AF65 is dispensable. A mechanism for the activity of SPF45-UHM could thus be engaging in ULM interactions and thus interfering with the network of interactions that initiate the assembly of the spliceosome at the 3´splice site, as described above. In the third article, we describe an unusual flexible homodimerization mode of the UHM in the splicing factor Puf60, which enables simultaneous interactions with ULM sequences on other splicing factors. I could show that the NMR relaxation properties of Puf60-UHM are inconsistent with a model of a rigid dimer, but rather indicate a dimerization via a flexible linker. I identified a flexible loop in the peptide backbone of Puf60-UHM, and showed that mutiation of acidic residues in this loop impairs the dimerization. To analyze the dimerization interface in further detail, I solved the structure of Puf60-UHM by X-ray crystallography. The acidic residues in the flexible loop of one UHM dimer subunit mediate the dimerization by contacting basic residues on the β-sheet surface of the other dimer subunit. Differences in the four dimer interfaces observed for the eight molecules in the asymmetric unit of the crystal support the model of an undescribed, flexible mode of dimerization, and thus complement the NMR relaxation data. Furthermore, I could show that the Puf60-UHM dimer and U2AF65-UHM contact different ULM sequences on the SF3b155 N-terminus in vitro, thus providing a possible explanation for the mutual cooperative activation of Puf60 and U2AF65 in splicing assays described in the literature. The fourth article is a review about recent research on the recognition of DNA double strand breaks (DSB) by covalent histone modifications. The p53 binding protein 1 (53BP1) is a DSB sensor and a checkpoint protein for mitosis. Recent crystallographic evidence indicates that 53BP1 recognizes DSB sites by binding histone H4 dimetylated at lysine 20 (H4-K20). We provide a comprehensive overview of the atomic resolution structures that revealed how proteins can specifically recognize histone tail modifications, especially methylated lysines, to read the information stored in what is called the histone code.
On the role of syntactic locality in morphological processes : the case of (Greek) derived nominals
(2008)
The paper is structured as follows. In section 2, I briefly summarize the facts on English and Greek nominalizations. In section 3, I discuss English nominal derivation in some detail. In section 4, I turn to the question of licensing of AS in nominals. In section 5, I turn to the issue of the optionality of licensing of AS in the nominal system.
This paper investigates the relation between TT-MCTAG, a formalism used in computational linguistics, and RCG. RCGs are known to describe exactly the class PTIME; simple RCG even have been shown to be equivalent to linear context-free rewriting systems, i.e., to be mildly context-sensitive. TT-MCTAG has been proposed to model free word order languages. In general, it is NP-complete. In this paper, we will put an additional limitation on the derivations licensed in TT-MCTAG. We show that TT-MCTAG with this additional limitation can be transformed into equivalent simple RCGs. This result is interesting for theoretical reasons (since it shows that TT-MCTAG in this limited form is mildly context-sensitive) and, furthermore, even for practical reasons: We use the proposed transformation from TT-MCTAG to RCG in an actual parser that we have implemented.
The Kaiserchronik is generically puzzling. In essence it is a spiritual world chronicle, but it lacks the usual historiographical systematisations of its theological content. However it does have three disputations, an unusual feature in a chronicle which has to date not been adequately explained. This essay argues, on the basis of comparisons with works in other literary forms, that these passages function as key expressions of the controlling idea of the entire work, namely the progress of the Gospel from the heathen to the Christian Empire, and that they are strategically located within the chronicle at the turning points in the success of Christian mission.
This paper deals with the variable position of adjectives in the Romanian DP. As all other Romance languages, Romanian allows for adjectives to appear in both prenominal and post-nominal position. In addition, however, Romanian has a third pattern: the so-called cel construction, in which the adjective in the post-nominal position is preceded by a determiner-like element, cel. This pattern is superficially similar to Determiner Spreading in Greek. In this paper we contrast the cel construction to Greek DS and discuss the similarities and differences between the two. We then present an analysis of cel as involving an appositive specification clause, building on de Vries (2002). We argue that the same structure is also involved in the context of nominal ellipsis, the second environment in which cel is found.
By translocating proteasomal degradation products into the endoplasmic reticulum (ER) for loading of major histocompatibility complex (MHC) class I molecules, the ATP binding cassette (ABC) transporter associated with antigen processing (TAP) plays a pivotal role in the adaptive immunity against infected or malignantly transformed cells. A key question regarding the transport mechanism is how the inter-domain communication and conformational dynamics of the TAP complex are connected during the peptide transport. To identify residues involved in this processes, we evolved a Trojan horse strategy in which a small artificial protease is inserted into antigenic epitopes. After binding, the TAP backbone in contact is cleaved, allowing the peptide sensor site to be mapped by mass spectrometry. Within this study, the peptide sensor and transmission interface have been identified. This region aligns with the cytosolic loop 1 (CL1) of Sav1866 and MsbA. Based on a number of experimental data and the homology to the bacterial ABC exporter Sav1866, we constructed a 3D structural model of the core TAP complex. According to this model, the CL1 and CL2 of TAP1 are extended cytosolic loops connecting the transmembrane helices (TMH) 2 and 3, and TMH4 and 5 respectively, and contact both nucleotide binding domains (NBDs) of the opposite subunit. In contrast to exporters, the cytosolic loop (named L-loop) of BtuCD importer is much shorter, and contacts only one NBD. The data confirm that the CL1 of TAP1 functions as signal transducer in ABC exporters, because it does not interfere with substrate binding but with substrate transport. The peptide contact site identified herein is restructured during the ATP hydrolysis cycle. Importantly, TAP showed a structural change trapped in the ATP hydrolysis transition state, because direct contact between peptide and CL1 is abolished. By cysteine scanning, the most conserved residues within CL1 were identified, which disrupted the tight coupling between peptide binding and transport. Together with Val-288, these residues are essential in sensing the bound peptide and inter-domain signal transmission. To characterize the molecular architecture of CL1, a convenient and minimally perturbing approach was used, which combined cysteine substitution in the CL1 region and determination of accessibility to thiol specific compounds with different properties. These studies revealed that the N-terminal region of CL1 has a good accessibility for hydrophilic (iodoacetamidofluorescein, IAF) and amphiphilic probes (BODIPY maleimide, BM), whereas the C-terminal region is accessible for hydrophobic probe (coumarin maleimide, CM). Kinetic studies of fluorescence labeling suggest that this region displayed a different accessibility to probes when the protein undergoes distinct conformations (e. g. nucleotide free state), thereby reflecting conformational transitions. Fluorescence labeling with BM induces a lost of peptide transport, whereas the peptide binding remains unaffected. These results indicate that covalent modifications of the CL1 residues influenced the inter-domain communication between transmembrane domain (TMD) and NBD. The X-loop is a recently discovered motif in the NBD of ABC exporters, which stays in close contact to the CLs. Moreover, because the X-loop precedes the ABC signature motif, it probably responds to ATP binding and hydrolysis and may transmit conformational changes to the CLs. By substitution of the highly conserved Glu-602 of TAP2 with residues that have different chemical properties, it was shown for the first time that the X-loop is a functional important element, which plays an key role in coupling substrate binding to downstream events in the transport cycle. We further verified domain swapping in the TAP complex by cysteine cross-linking. The TAP complex can be reversibly arrested either in a binding or translocation incompetent state by cross-linking of the X-loop to CL1 or CL2, respectively. These results resolve the structural arrangement of the transmission interface and point to different functions of the cytosolic loops in substrate recognition, signaling and transport.
We argue for incorporating the financial economics of market microstructure into the financial econometrics of asset return volatility estimation. In particular, we use market microstructure theory to derive the cross-correlation function between latent returns and market microstructure noise, which feature prominently in the recent volatility literature. The cross-correlation at zero displacement is typically negative, and cross-correlations at nonzero displacements are positive and decay geometrically. If market makers are sufficiently risk averse, however, the cross-correlation pattern is inverted. Our results are useful for assessing the validity of the frequently-assumed independence of latent price and microstructure noise, for explaining observed cross-correlation patterns, for predicting as-yet undiscovered patterns, and for making informed conjectures as to improved volatility estimation methods.
In this paper it is argued that several typologically unrelated languages share the tendency to avoid voiced sibilant affricates. This tendency is explained by appealing to the phonetic properties of the sounds, and in particular to their aerodynamic characteristics. On the basis of experimental evidence it is shown that conflicting air pressure requirements for maintaining voicing and frication are responsible for the avoidance of voiced affricates. In particular, the air pressure released from the stop phase of the affricate is too high to maintain voicing which in consequence leads to a devoicing of the frication part.
In this paper it is argued that several typologically unrelated languages share the tendency to avoid voiced sibilant affricates. This tendency is explained by appealing to the phonetic properties of the sounds, and in particular to their aerodynamic characteristics. On the basis of experimental evidence it is shown that conflicting air pressure requirements for maintaining voicing and frication are responsible for the avoidance of voiced affricates. In particular, the air pressure released from the stop phase of the affricate is too high to maintain voicing which in consequence leads to a devoicing of the frication part.
Various concurrency primitives have been added to sequential programming languages, in order to turn them concurrent. Prominent examples are concurrent buffers for Haskell, channels in Concurrent ML, joins in JoCaml, and handled futures in Alice ML. Even though one might conjecture that all these primitives provide the same expressiveness, proving this equivalence is an open challenge in the area of program semantics. In this paper, we establish a first instance of this conjecture. We show that concurrent buffers can be encoded in the lambda calculus with futures underlying Alice ML. Our correctness proof results from a systematic method, based on observational semantics with respect to may and must convergence.
This paper proves several generic variants of context lemmas and thus contributes to improving the tools for observational semantics of deterministic and non-deterministic higher-order calculi that use a small-step reduction semantics. The generic (sharing) context lemmas are provided for may- as well as two variants of must-convergence, which hold in a broad class of extended process- and extended lambda calculi, if the calculi satisfy certain natural conditions. As a guide-line, the proofs of the context lemmas are valid in call-by-need calculi, in callby-value calculi if substitution is restricted to variable-by-variable and in process calculi like variants of the π-calculus. For calculi employing beta-reduction using a call-by-name or call-by-value strategy or similar reduction rules, some iu-variants of ciu-theorems are obtained from our context lemmas. Our results reestablish several context lemmas already proved in the literature, and also provide some new context lemmas as well as some new variants of the ciu-theorem. To make the results widely applicable, we use a higher-order abstract syntax that allows untyped calculi as well as certain simple typing schemes. The approach may lead to a unifying view of higher-order calculi, reduction, and observational equality.
We provide the first non-trivial result on dynamic breadth-first search (BFS) in external-memory: For general sparse undirected graphs of initially $n$ nodes and O(n) edges and monotone update sequences of either $\Theta(n)$ edge insertions or $\Theta(n)$ edge deletions, we prove an amortized high-probability bound of $O(n/B^{2/3}+\sort(n)\cdot \log B)$ I/Os per update. In contrast, the currently best approach for static BFS on sparse undirected graphs requires $\Omega(n/B^{1/2}+\sort(n))$ I/Os. 1998 ACM Subject Classification: F.2.2. Key words and phrases: External Memory, Dynamic Graph Algorithms, BFS, Randomization.
In the article, a travel sketch of Danish playwright Kaj Munk (1898 – 1944) is analytically considered. The analysis of this text allows drawing at least three conclusions: 1. Explicit motive of seasickness, figuring here as antithetic modification of implicite present free-standing posture motive, symbolizes idea of disintegrating personality. 2. Such a symbolism is deeply rooted in that of Danish identity. 3. From literary styles and trends history point of view, the sketch appears to be typical of that line in expressionism, which continues tradition of symbolism as artistic and literary trend of late 19th century.
Agglutinated foraminiferal assemblages from the Oligocene section of an exploration well drilled in the distal part of the Congo Fan are fully documented and interpreted for palaeoenvironment. A total of 65 ditch cutting samples were analysed at 10 m intervals, from 3630 to 4270 m below rotary table. An average of 170 specimens were extracted per sample, with over 100 species being documented and described using SEM and light photography. The results reveal the most taxonomically diverse deepsea Oligocene fauna yet described. Six assemblages have been defined and analysed with Correspondence and 'Morphogroup' Analysis. These are 1. Nothia robusta / Reticulophragmium Assemblage (4110-4270 m), 2. Nothia robusta / Scherochorella congoensis / Discammilloides sp. 1 Assemblage (4000-4100 m), 3. High diversity Reticulophragmium Assemblage (3870-3990 m), 4. Portatrochammina profunda Assemblage (3790-3860 m), 5. Nothia latissima Assemblage (3730-3780 m) and 6. Low abundance Assemblage (3630-3720 m). Palaeobathymetric estimates range from middle -lower bathyal based on comparison with living taxa and morphogroup distributions. These results extend the known stratigraphic range (last occurrences) of Reticulophragmium amp/eetens into the Oligocene in the Atlantic, and possibly also Paratrochamminoides gorayskii, Paratrochamminoides olszewskii, Trochamminoides aff. proteus, Trochamminoides subcoronatus, Haplophragmoides horridus and Haplophragmoides walteri, although reworking is documented with these species. Results also extend the known first occurrences of Recurvoides azuaensis, Spiropsammina primula, Cyclammina aff. orbicularis, Discamminoides sp. and Glaphyrammina americana into the Oligocene. Large scale variations within faunas are largely assigned to documente d variations in sand content, where higher proportions of sand generally coincide with reduced diversity and abundance along with a dominance of opportunistic species such as Nothia robusta, Nothia latissima and Ammodiscus latus. A major excursion in the infaunal morpho group, suspension-feeding morpho group and diversity and abundance within Assemblage 2 is termed the 'Scherochorella Event', and does not correlate with an increase in sand. This fauna is thought to be the result of lower oxygen conditions allowing the dominance of the low oxygen morphotype Scherochorella congoensis and the opportunistic species Nothia robusta. Deep-water circulation in the Atlantic at this time is generally thought to have been strong, and this event suggests that there may have been a temporary expansion of the oxygen minimum zone during the Late Oligocene, coinciding with increased benthic 8180 values, global cooling, and increased upwelling associated with a stronger polar front. The otherwise high diversity of the fauna in the well supports the interpretation of well-oxygenated conditions.
Aramaic is not among the oldest Semitic languages in a strictly chronological sense, but among those languages which are still spoken today, it has the longest continuous written tradition. The existing written documents span a period of three millennia and thus enable us to study language history in a long-term perspective. It is very important, in this respect, that the latest stage of development of Aramaic, Neo-Aramaic, still exists in a multitude of spoken varieties which can be studied in vivo. We can thus describe the phonetics and phonology of the modern varieties with more precision than is possible for the older language stages, which in turn enables us to draw conclusions on diachronic sound change. Likewise, we can study morphology and syntax not only from recorded texts, but we also have recourse to native speakers in order to clarify doubtful points. Thus the latest stage of Aramaic casts a strong light back into the past. It is therefore most unfortunate that many Aramaicists and Syrologists show so little interest in this living heritage.
Friedrich Schlegel's lasting contribution to linguistics is usually seen in the impact that his book "Über die Sprache und Weisheit der Indier" from 1808 left on comparative linguistics and on the study of Sanskrit. Schlegel was one of the first European scholars to have studied Sanskrit extensively and he made a number of translations of Sanskrit literature into German which make up one third of "Über die Sprache und Weisheit der Indier". Schlegel's book is widely regarded as a founding document both of comparative linguistics and of indology, a fact which is quite remarkable in light of the development of Schlegel's thought after this text. His interest in Indian studies ceased more or less directly with the publication of this work, while his thoughts on language became more and more suffused by transcendental philosophy.
Extracts of Boswellia serrata, also known as Indian frankincense, have been used to treat inflammatory diseases in the Indian ayurvedic medicine or Chinese traditional medicine (TCM) for over 3000 years, but the molecular mechanisms of the anti-inflammatory effects are still not well understood. It is obvious that the boswellic acids, the major compounds in the extracts, are responsible for the efficacy. This work employed a protein fishing technique to identify putative targets of boswellic acids at different stages within the inflammatory cascade. For fishing experiments, boswellic acids were immobilized to sepharose and incubated with cell lysates. After washing and boiling, fished proteins were separated by SDS-PAGE and analysed by MALDI-TOF-MS. CatG, DNA-PK and the protein kinase Akt were identified by protein pulldowns with immobilised BAs and characterised as selective and important targets for BAs with an IC50 in the range of physiologically achievable plasma levels up to 5 microM. In addition, the influence on several signal transductions by BAs was tested. Calcium influx, arachidonic acid release, platelet aggregation and TNFalpha-release were assayed to reveal further pharmacological effects of BAs. Celecoxib is a well-known selective COX-2 inhibitor that is in clinical use. In this work, it is demonstrated that celecoxib is also a highly potent direct 5-LO inhibitor. Celecoxib is used in arthritis and its gastro-intestinal side effects are reduced compared to non-selective NSAIDs. In patients with a familiar disposition to polyp forming, celecoxib reduced polyps and the incidence of colon cancer. Because of lowered leukotriene levels in patients under celecoxib therapy it was plausible to test whether celecoxib interferes with 5-LO. Here it is shown that the activity of 5-LO is inhibited in PMNL and cell-free assays with IC50 of 8 microM in intact cells, 20 microM with supplemented arachidonic acid and 30 microM in cell-free systems. Thus, celecoxib is a dual inhibitor of COX-2 and 5-LO. Since 2006, celecoxib has been approved as an orphan drug for the treatment of familial adenomatous polyposis. Aside from this indication, it could be useful for treatment of asthma and other diseases where 5-LO is implicated.
Jüdische Grabsteinepigraphik: R. Yosef Trani (1568-1639), R. Akiva Eger (d. 1837), R. David Hoffmann (d. 1921)